A computational approach: proposing potential inhibitors by targeting SRC/BCR-ABL Kinase in Acute lymphoblastic leukemia through drug repurposing

Abstract

Acute lymphoblastic leukemia (ALL) is a hematological malignancy characterized by the overproduction of immature white blood cells. Patients with Philadelphia chromosome-positive ALL (Ph+ ALL) face significant challenges, including drug resistance and disease relapse, primarily driven by the BCR-ABL fusion protein. This study investigates 500 FDA-approved drugs to identify potential candidates for repurposing. The goal was to find drugs that can inhibit the SRC/BCR-ABL protein. Molecular docking was carried out using dasatinib, a known inhibitor of the protein as a reference. The analysis found several candidates with superior binding affinities compared to dasatinib. Six drugs were selected based on their superimposition to the reference drug and interaction profiles. They are acarbose (anti-diabetic), amrubicin (anti-neoplastic), cetirizine (antihistamine), dabrafenib (anti-neoplastic), streptomycin (anti-mycobacterial), and teniposide (anti-neoplastic). These findings suggest promising alternatives for targeting the BCR-ABL fusion protein, necessitating further experimental validation through in vitro and in vivo studies to confirm their efficacy and safety.